Quetiapine is in clinical development by Zeneca Pharmaceuticals, for the treatment of subjects with schizophrenia and other psychotic disorders. The primary objective of this trial is to compare safety and tolerability of quetiapine to risperidone in a broad outpatient population of individuals with schizophrenia and other psychotic disorders. This secondary objective is to compare quality-of-life between patients treated with quetiapine and risperidone. Subjects will be randomzied and start therapy with open-label quetiapine or risperidone. Randomization will occur in a 3:1 ratio (quetiapine : risperidone). Cross-tapering of prior antipsychotics will take place over the first 2 weeks, not to exceed 1 month as per clinical judgment. The ultimate goal is monotherapy. The assistance of the GCRC is requested to assist with blood draws at screening.